This study is designed to provide basic information regarding host- pathogen interactions while addressing the clinically significant problems of respiratory tract infection with non-encapsulated Haemophilus influenzae. The underlying premise is that in patients where infection with this organism does occur, there may be aspects of the normal respiratory mucociliary clearance mechanism which may be positively altered to improve respiratory health and lesson the opportunity and persistence of infection. The specific aims of this proposal focus on describing the mechanisms of interactions of non-encapsulated Haemophilus influenzae with human respiratory mucins. Adherence assays will be employed to describe the interactions of existing laboratory strains, fresh respiratory isolates, and mutant strains of non-encapsulated H. influenzae, with both normal and COPD derived mucin. Recombinant DNA techniques will then be applied for the development of mutant strains of mucin-binding organisms which are deficient in previously identified adhesins. Cloning and analysis of the DNA responsible for at least one of the remaining adhesins will further elucidate the mechanisms by which bacterial pathogens encounter their host. Mobilization of this adhesin gene into non mucin-binding strains of H. influenza and E. coli, adhesin genes have been inactivated, and screening for the prevalence of this and other known adhesins in clinical isolates, will address the relative contributions of this cloned gene product to the overall interactions of mucins and H. influenzae.